Previous work has defined that de novo phosphatidylcholine (PC) synthesis is regulated in intestinal mucosa by the PC concentration in the intestinal lumen and that phosphocholinetransferase is the primary enzyme to be affected by luminal PC perfusion. Therefore, this proposal first seeks to more clearly understand the alterations in the intestinal microsomal membrane which results in changes in enzyme activity since it has been established that luminal PC does not fundamentally change the enzyme but does alter microsomal permeability. Secondly, the effect of specific lipid alterations of the microsomal membrane on phosphocholinetransferase activity will be investigated. Thirdly, the effect of specific pathophysiologic states on phosphocholinetransferase activities and its ability to be regulated by luminal PC will be studied. The pathological states to be studied are alcohol ingestion, diabetes mellitus, hyperthyroidism and Addison's disease. The second part of this proposal concerns an exploration of the physiological role of a newly discovered, active phospholipase which is present in large amounts in intestinal mucosa and is secreted into the intestinal lumen. Its substrate specificity, phosphatidylglycerol (PG), while the enzyme is localized to the intestinal mucosa, suggests a relationship with either bacteria and/or vegetable matter since the cell walls of both contain PG. The effect on enzyme activity in intestinal mucosa and lumen of bacteria and vegetable matter within the lumen will be studied. If warranted by these experiments, two disease states will be studied in humans, Whipple's disease and Crohn's disease, to determine if this enzyme plays a role in the causation of these diseases.